Pemetrexed Diacid

Pemetrexed Diacid (also known as LY231514) is a pyrimidine-based folate analog that suppresses tumor growth by inhibiting both DNA synthesis and folate metabolism at multiple target enzymes. The multiple enzyme inhibition is unique, as methotrexate inhibits only dihydrofolate reductase, and 5-fluorouracil and raltitrexed inhibit only thymidine synthetase. Thus, Pemetrexed Diacid may be useful for 5-fluorouracil-, methotrexate-, and raltitrexed-resistant cancers. Pemetrexed Diacid has a wide range of anti-cancer activity against malignant mesothelioma, non-small cell lung cancer (NSCLC), and breast, colorectal, head and neck, gastric, bladder, renal cell, and pancreatic cancers. Pemetrexed Diacid plus cisplatin for chemonaive patients with malignant mesothelioma resulted in a median survival time of 12.1 months as compared with 9.3 months for recipients of cisplatin monotherapy; approximately 75% of patients had either stage 3 or 4 disease. Folic acid and vitamin B12 supplementations are needed to reduce toxicity and enable therapy continuation.

Pemetrexed Diacid’s innovator is Eli Lilly and appears world-wide under the brand name Alimta.

Pemetrexed Diacid acts as a 'multitargeted' antifolate compound by interrupting both purine synthesis via thymidylate synthase (TS) and dihydrofolate reductase (DHFR) inhibition, and pyrimidine synthesis via glycinamide ribonucleotide formyl transferase (GARFT) and aminoimidazole carboxamide formyl transferase (AICARFT) inhibition.
Inhibition of TS leads to a reduction in thymidine, which is needed for DNA synthesis. Additionally, inhibition of both GARFT and AICARFT, as intracellular Pemetrexed Diacid levels increase, prevents de novo purine biosynthesis, leading to further depletion of required cell precursors. Thus, both thymidine and hypoxanthine (a purine) are needed to rescue a cell from cytotoxicity from Pemetrexed Diacid.
The free level of Pemetrexed Diacid in the cell determines the rate of polyglutamation, thus the high affinity of Pemetrexed Diacid for the reduced folate carrier and for FPGS leads to a high rate of Pemetrexed Diacid polyglutamation. Natural folates within the cell modulate Pemetrexed Diacid activity by competing for polyglutamation by FPGS.
The tri- and penta-glutamated metabolites of Pemetrexed Diacid also inhibit TS, DHFR, GARFT, and, to a lesser extent, AICARFT. Similar to methotrexate, the tri- and penta-glutamated metabolites exhibit markedly higher antagonistic activity in folate-dependent enzymes, except for DHFR, than the parent drug, Pemetrexed monoglutamate.

Pemetrexed Diacid appears in the following formulation and dosage:
Intravenous powder for solution: 100 mg/vial and 500 mg/vial.

General data on Pemetrexed DiacidActive Pharmaceutical Ingredient

CAS Registry: 150399-23-8
ATC: L01BA04
Molecular Formula: C20H19N5Na2O6
Molecular Weight: 471.4

TAPI's Pemetrexed Diacid Pharmaceutical Ingredient

TAPI's Pemetrexed Diacid Active Pharmaceutical Ingredient is produced in Teva Pharmaceutical Works Limited in Debrecen, Hungary.

Pemetrexed Diacid is produced by TAPI by High Potent Technology synthesis and considered to be low volume Active Pharmaceutical Ingredient.

TAPI's Pemetrexed Diacid has unique features that might be advantage for final dosage development. TAPI has filed several patent applications for Pemetrexed Diacid. Please, see table below for issued patents and pending applications.

Other products, in the group of ANTINEOPLASTIC AGENTS - Miscellaneous antineoplastics derivatives available on TAPI's portfolio are:  Bicalutamide, Bortezomib, Etoposide, Fludarabine Phosphate and Fluorouracil.Contact us today for information on these products.

TAPI provide full service on Pemetrexed Diacid and other APIs in our portfolio. Our local sales offices provide full information on our product, regulatory compliance and documentation on Pemetrexed Diacid. Contact us today for further inquiries and samples and kilograms availability information for TAPI's Pemetrexed Diacid.

Legal Note

Product exploitation, including development, sales and offer for sale are performed where permissible by patent law. This presentation is not and should not constitute an offer for sale in territories where it is not permitted by law. In USA Products  that  Currently on Patent are available for R&D Use in Accordance with 35 USC §271 (e) (1).

*TAPI stands for Teva's Active Pharmaceutical Ingredients